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ZIOPHARM Completes Enrollment in Second Patient Cohort and Initiates Enrollment in Third Cohort in Phase 1 Study of Gene Therapy Candidate Ad-RTS-hIL-12 in Brain Cancer

On June 27, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new cancer immunotherapies, reported the successful completion of enrollment in the first and second dosing cohorts as well as the initiation of enrollment in a third cohort in the Company’s ongoing multi-center Phase 1 study of Ad-RTS-hIL-12 + orally administered veledimex to treat recurrent or progressive glioblastoma (GBM) or grade III malignant glioma (Press release, Ziopharm, JUN 27, 2016, View Source [SID:1234513578]). Ad-RTS-hIL-12 + veledimex is a novel viral gene therapy candidate for the controlled expression of interleukin 12 (IL-12), a critical protein for stimulating an anti-cancer immune response.

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The primary objective of the study is to determine the safety and tolerability of a single intratumoral Ad-RTS-hIL-12 injection activated upon dosing with oral veledimex. Secondary objectives are to determine the maximum tolerated dose, the immune responses elicited, and assessment of biologic response. The first cohort of seven patients received 20 mg doses of veledimex, the second cohort of six patients received 40 mg doses of veledimex, and the third cohort will receive 30 mg doses of veledimex to refine the effect of activating the immune response within the tumor. The resultant immunologic activity that follows IL-12 expression in the brain suggests that no further dose escalation will be necessary and the optimal dosing may be reached sooner than initially anticipated.

Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM, commented: "With the RheoSwitch (RTS) technology, the only switch currently in the clinic that operates on gene transcription, we have demonstrated the ability for veledimex to cross the human blood brain barrier and activate production of IL-12 in GBM tumors in a dose-dependent manner, giving us the potential to precisely tune the balance between activity and tolerability."

Data from 11 patients with recurrent high-grade gliomas were recently presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. All of these patients failed at least two prior lines of therapy and underwent partial resection leaving residual tumors, in certain cases with significant tumor burden. Ad-RTS-hIL-12 was administered through direct injection into the brain tumor and veledimex was taken orally to activate the production of IL-12 from the tumor site and stimulate an immune response.

As of May 18th, the date of data collection for the ASCO (Free ASCO Whitepaper) presentation, overall median follow up was 6.2 months, with 10 of 11 recipients alive. IL-12 in the bloodstream was measured and was found to be proportional to the amount of veledimex administered, demonstrating that this orally-delivered activator crossed the blood brain barrier to turn on the RheoSwitch technology in a dose-dependent manner.

To date, toxicities in both dose cohorts were consistent with those previously reported, with a higher incidence of grade 3 or greater adverse events in the 40 mg dose group. All related side effects were reversed upon cessation of veledimex. No subsequent deaths have been reported.

The Company expects to present updated results from the study at a scientific meeting later in the year.

"Overall survival remains the gold standard of therapeutic success in glioblastoma, particularly in high-grade, recurrent disease, where survival is too often measured by just a few months," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "We remain encouraged by the outcomes of Ad-RTS-hIL-12 as a single agent tuning the immune system in this GBM study. We believe that these early results also have positive implications for our combination approach utilizing this novel gene therapy with immune check point inhibitors. We look forward to additional follow up as we work to fine-tune dosing levels using the RheoSwitch technology."

Ad-RTS-hIL-12 + veledimex has been granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with malignant glioma.

About Glioblastoma

Glioblastoma is an aggressive primary brain tumor affecting approximately 74,000 people worldwide each year.i, ii Recurrent glioblastoma is an aggressive cancer with one of the lowest 3-year survival rates, at 3%, among all cancers.iii For patients who have experienced multiple recurrences the prognosis is particularly poor, with a median overall survival (OS) of 6-7 months, while OS in patients that have failed temozolomide and bevacizumab, or equivalent salvage chemotherapy, is approximately 3-5 months.iv, v

LabCorp Announces Launch of New Companion Diagnostic for Non-Small Cell Lung Cancer

On June 27, 2016 Laboratory Corporation of America Holdings (LabCorp) (NYSE: LH) reported the availability of a new application for the companion diagnostic associated with the use of Tarceva for the treatment of certain patients with non-small cell lung cancer (NSCLC) (Press release, LabCorp, JUN 27, 2016, View Source [SID:1234513576]). The Roche cobas EGFR Mutation Test v2 is the first blood-based test approved for clinical use in the U.S. to detect certain epidermal growth factor receptor (EGFR) gene mutations in NSCLC patients. LabCorp played a key role in making the test available upon approval by the U.S. Food and Drug Administration (FDA) and is the only national laboratory currently offering the test.

“The availability of this test demonstrates LabCorp’s industry-leading position in the commercialization of companion diagnostics,” said David P. King, chairman and chief executive officer of LabCorp. “The success and growth of our companion diagnostics business continues to differentiate us from our competitors as we carry out our mission to improve health and improve lives.”

The cobas EGFR Mutation Test v2, which was approved by the FDA on June 1, 2016, can be used on either plasma obtained from a routine blood collection or on tumor tissue obtained from a surgical biopsy. The test identifies epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) substitution mutations in patients with NSCLC who may benefit from first-line treatment with Tarceva. The availability of a less-invasive, blood-based test gives physicians a powerful new treatment option for patients who may not be able to undergo surgical biopsy or who cannot provide a tumor specimen for other reasons.

“The FDA approval of the cobas EGFR Mutation Test v2 for plasma-based testing offers a minimally invasive option for patients with NSCLC,” said Uwe Oberlaender, Head of Roche Molecular Diagnostics. “Partnering with key labs ensures that patients can be tested conveniently.”

“LabCorp is pleased to add this important new test to our menu of world-class diagnostics,” said Marcia Eisenberg, Ph.D., chief scientific officer of LabCorp Diagnostics. “Knowledge is power for patients and their physicians, and tests like this can help patients access targeted, personalized treatment.”

Lung cancer is the leading cause of cancer death in the U.S. among both men and women, accounting for about one-third of all cancer deaths, more than the other common cancers combined (breast, prostate and colon cancers). More than 80% of all lung cancers in the US are NSCLC, and 10%-20% of these have EGFR mutations.

The cobas EGFR Mutation Test v2 is now available for patient testing nationwide from LabCorp and Integrated Oncology, a member of the LabCorp Specialty Testing Group.

Tarceva is developed and commercialized by Astellas Pharma US in partnership with Genentech in the United States, Chugai in Japan and Roche in the rest of the world.

COBAS is a registered trademark of Roche.

Tarceva is a registered trademark of OSI Pharmaceuticals.

LabCorp Announces Launch of New Companion Diagnostic for Non-Small Cell Lung Cancer

The Roche cobas EGFR Mutation Test v2 is the first blood-based test approved for clinical use in the U.S. to detect certain epidermal growth factor receptor (EGFR) gene mutations in NSCLC patients. LabCorp played a key role in making the test available upon approval by the U.S. Food and Drug Administration (FDA) and is the only national laboratory currently offering the test.

"The availability of this test demonstrates LabCorp’s industry-leading position in the commercialization of companion diagnostics," said David P. King, chairman and chief executive officer of LabCorp. "The success and growth of our companion diagnostics business continues to differentiate us from our competitors as we carry out our mission to improve health and improve lives."

The cobas EGFR Mutation Test v2, which was approved by the FDA on June 1, 2016, can be used on either plasma obtained from a routine blood collection or on tumor tissue obtained from a surgical biopsy. The test identifies epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) substitution mutations in patients with NSCLC who may benefit from first-line treatment with Tarceva. The availability of a less-invasive, blood-based test gives physicians a powerful new treatment option for patients who may not be able to undergo surgical biopsy or who cannot provide a tumor specimen for other reasons.

"The FDA approval of the cobas EGFR Mutation Test v2 for plasma-based testing offers a minimally invasive option for patients with NSCLC," said Uwe Oberlaender, Head of Roche Molecular Diagnostics. "Partnering with key labs ensures that patients can be tested conveniently."

"LabCorp is pleased to add this important new test to our menu of world-class diagnostics," said Marcia Eisenberg, Ph.D., chief scientific officer of LabCorp Diagnostics. "Knowledge is power for patients and their physicians, and tests like this can help patients access targeted, personalized treatment."

Lung cancer is the leading cause of cancer death in the U.S. among both men and women, accounting for about one-third of all cancer deaths, more than the other common cancers combined (breast, prostate and colon cancers). More than 80% of all lung cancers in the US are NSCLC, and 10%-20% of these have EGFR mutations.

The cobas EGFR Mutation Test v2 is now available for patient testing nationwide from LabCorp and Integrated Oncology, a member of the LabCorp Specialty Testing Group.

Tarceva is developed and commercialized by Astellas Pharma US in partnership with Genentech in the United States, Chugai in Japan and Roche in the rest of the world.

COBAS is a registered trademark of Roche.

Tarceva is a registered trademark of OSI Pharmaceuticals.

Puma Biotechnology Submits Marketing Authorization Application for PB272 (Neratinib) as Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer in Europe

On June 27, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported that it has submitted its Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for neratinib (Press release, Puma Biotechnology, JUN 27, 2016, View Source [SID:1234513557]). The potential indication is for the extended adjuvant treatment of HER2-positive early stage breast cancer that has previously been treated with trastuzumab (Herceptin)-based adjuvant therapy. The submission is based upon the ExteNET Phase III study, which reached its primary endpoint whereby neratinib demonstrated a statistically significant reduction of risk of invasive disease recurrence or death versus placebo.

“Although the use of trastuzumab in the adjuvant setting has led to a reduction in disease recurrence in patients with early stage HER2-positive breast cancer, there remains an unmet clinical need for further improvement in outcome in order to attempt to further reduce this risk of recurrence following trastuzumab therapy,” said Alan H. Auerbach, Chief Executive Officer and President of Puma. “Neratinib may be able to provide this type of improvement to further help the patients with this disease. We look forward to working with the CHMP/EMA during their review of this submission. This submission marks the first step in the broader global registration plan for neratinib and Puma is working with the U.S. FDA on the U.S. NDA, the next submission currently anticipated in mid-2016.”

In the ExteNET study, treatment with neratinib resulted in a 33% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.67, p = 0.009). The 2-year invasive disease free survival (DFS) rate for the neratinib arm was 93.9% and the 2-year DFS rate for the placebo arm was 91.6%. For the pre-defined subgroup of patients with hormone receptor positive disease, the results of the trial demonstrated that treatment with neratinib resulted in a 49% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.51, p = 0.001). For the patients with hormone receptor positive disease, the 2-year DFS rate for the neratinib arm was 95.4% and the 2-year DFS rate for the placebo arm was 91.2%. Results of the study were published online in The Lancet Oncology on February 10, 2016.

The most frequently observed adverse event for the neratinib-treated patients was diarrhea, with approximately 39.9% of the neratinib-treated patients experiencing grade 3 or higher diarrhea (1 patient (0.1%) had grade 4 diarrhea). Patients who received neratinib in the ExteNET trial did not receive any prophylaxis with antidiarrheal agents to prevent the neratinib-related diarrhea. Interim results of a Phase II study of neratinib monotherapy in patients with HER2-positive early stage breast cancer who have previously been treated with adjuvant trastuzumab, where patients received anti-diarrheal prophylaxis with loperamide, demonstrated that treatment with prophylactic loperamide reduced the rate of grade 3 or higher diarrhea to between 13.0% and 18.5%.

About ExteNET

The ExteNET trial is a double-blind, placebo-controlled, Phase III trial of neratinib versus placebo after adjuvant treatment with trastuzumab (Herceptin) in women with early stage HER2-positive breast cancer. The trial randomized 2,840 patients in 41 countries with early stage HER2-positive breast cancer who had undergone surgery and adjuvant treatment with trastuzumab. After completion of adjuvant treatment with trastuzumab, patients were randomized to receive extended adjuvant treatment with either neratinib or placebo for a period of one year. Patients were then followed for recurrent disease, ductal carcinoma in situ (DCIS), or death for a period of two years after randomization in the trial. The primary endpoint of the trial was DFS.

Puma Biotechnology Submits Marketing Authorization Application for PB272 (Neratinib) as Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer in Europe

The potential indication is for the extended adjuvant treatment of HER2-positive early stage breast cancer that has previously been treated with trastuzumab (Herceptin)-based adjuvant therapy. The submission is based upon the ExteNET Phase III study, which reached its primary endpoint whereby neratinib demonstrated a statistically significant reduction of risk of invasive disease recurrence or death versus placebo.

"Although the use of trastuzumab in the adjuvant setting has led to a reduction in disease recurrence in patients with early stage HER2-positive breast cancer, there remains an unmet clinical need for further improvement in outcome in order to attempt to further reduce this risk of recurrence following trastuzumab therapy," said Alan H. Auerbach, Chief Executive Officer and President of Puma. "Neratinib may be able to provide this type of improvement to further help the patients with this disease. We look forward to working with the CHMP/EMA during their review of this submission. This submission marks the first step in the broader global registration plan for neratinib and Puma is working with the U.S. FDA on the U.S. NDA, the next submission currently anticipated in mid-2016."

In the ExteNET study, treatment with neratinib resulted in a 33% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.67, p = 0.009). The 2-year invasive disease free survival (DFS) rate for the neratinib arm was 93.9% and the 2-year DFS rate for the placebo arm was 91.6%. For the pre-defined subgroup of patients with hormone receptor positive disease, the results of the trial demonstrated that treatment with neratinib resulted in a 49% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.51, p = 0.001). For the patients with hormone receptor positive disease, the 2-year DFS rate for the neratinib arm was 95.4% and the 2-year DFS rate for the placebo arm was 91.2%. Results of the study were published online in The Lancet Oncology on February 10, 2016.

The most frequently observed adverse event for the neratinib-treated patients was diarrhea, with approximately 39.9% of the neratinib-treated patients experiencing grade 3 or higher diarrhea (1 patient (0.1%) had grade 4 diarrhea). Patients who received neratinib in the ExteNET trial did not receive any prophylaxis with antidiarrheal agents to prevent the neratinib-related diarrhea. Interim results of a Phase II study of neratinib monotherapy in patients with HER2-positive early stage breast cancer who have previously been treated with adjuvant trastuzumab, where patients received anti-diarrheal prophylaxis with loperamide, demonstrated that treatment with prophylactic loperamide reduced the rate of grade 3 or higher diarrhea to between 13.0% and 18.5%.

About ExteNET

The ExteNET trial is a double-blind, placebo-controlled, Phase III trial of neratinib versus placebo after adjuvant treatment with trastuzumab (Herceptin) in women with early stage HER2-positive breast cancer. The trial randomized 2,840 patients in 41 countries with early stage HER2-positive breast cancer who had undergone surgery and adjuvant treatment with trastuzumab. After completion of adjuvant treatment with trastuzumab, patients were randomized to receive extended adjuvant treatment with either neratinib or placebo for a period of one year. Patients were then followed for recurrent disease, ductal carcinoma in situ (DCIS), or death for a period of two years after randomization in the trial. The primary endpoint of the trial was DFS.